Brandon S Klinedinst1, Colleen Pappas2, Scott Le3, Shan Yu4, Qian Wang1, Li Wang4, Karin Allenspach-Jorn5, Jonathan P Mochel6, Auriel A Willette7. 1. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA; Neuroscience Graduate Program, Iowa State University, Ames, IA, USA. 2. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA. 3. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA; Interdisciplinary Graduate Studies Program, Iowa State University, Ames, IA, USA. 4. Department of Statistics, Iowa State University, Ames, IA, USA. 5. Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA. 6. Department of Biomedical Sciences, Iowa State University, Ames, IA, USA. 7. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA; Neuroscience Graduate Program, Iowa State University, Ames, IA, USA; Interdisciplinary Graduate Studies Program, Iowa State University, Ames, IA, USA; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA; Department of Neurology, University of Iowa, Iowa City, USA. Electronic address: awillett@iastate.edu.
Abstract
BACKGROUND: Obesity in midlife and early late-life is associated with worse normal cognitive aging. Dual-energy X-ray absorptiometry (DEXA) suggests that visceral adipose mass (VAM) plays a predominant role, whereas non-visceral adipose mass (NVAM) and lean muscle mass (LMM) have shown conflicting relationships. It is unknown how longitudinal, cognitive changes in age-sensitive domains like fluid intelligence (FI) correspond to VAM, NVAM, and LMM in women and men. Furthermore, changes over time in blood leukocyte sub-populations may partially or fully account for sex-specific associations. METHODS: Data on 4431 late middle-aged, cognitively unimpaired adults (mean = 64.5 y) was obtained from the UK Biobank prospective cohort across 22 centers. FI scores, blood leukocyte counts, and covariates (age, social class, education) were measured at three 2-year intervals over 6 years. DEXA collection overlapped with these intervals. Sex-stratified growth curves, structural equations, and Preacher-Hayes mediation were used to estimate direct and indirect effects. β-weights were standardized. RESULTS: More LMM predicted gains in FI scores among women (β = 0.130, p < .001) and men (β = 0.089, p < .001). Conversely, more VAM and NVAM independently predicted FI decline equally among sexes (e.g., NVAM: women: β = -0.082, p < .001; men: β = -0.076, p < .001). Among women, FI associations were fully mediated by higher eosinophil counts via VAM (λ = 30.8%, p = .028) and lower lymphocyte counts via LMM (λ = 69.2%, p = .021). Among men, FI associations were partially mediated by lower basophils counts via LMM (λ = 4.5%, p = .042) and higher counts via VAM (λ = 50%, p = .037). CONCLUSION: The proportion of LMM and VAM equally influenced male FI changes over 6 years, whereas higher LMM among women appeared to more strongly influence. FI changes. Leukocyte counts strongly mediated VAM- and LMM-related FI changes in a sex-specific manner, but not for NVAM. For clinical translation, exercise studies in older adults may benefit from assessing sex-specific values of DEXA-based tissue mass, FI, and leukocyte sub-populations to gauge potential cognitive benefits of less VAM and more LMM.
BACKGROUND:Obesity in midlife and early late-life is associated with worse normal cognitive aging. Dual-energy X-ray absorptiometry (DEXA) suggests that visceral adipose mass (VAM) plays a predominant role, whereas non-visceral adipose mass (NVAM) and lean muscle mass (LMM) have shown conflicting relationships. It is unknown how longitudinal, cognitive changes in age-sensitive domains like fluid intelligence (FI) correspond to VAM, NVAM, and LMM in women and men. Furthermore, changes over time in blood leukocyte sub-populations may partially or fully account for sex-specific associations. METHODS: Data on 4431 late middle-aged, cognitively unimpaired adults (mean = 64.5 y) was obtained from the UK Biobank prospective cohort across 22 centers. FI scores, blood leukocyte counts, and covariates (age, social class, education) were measured at three 2-year intervals over 6 years. DEXA collection overlapped with these intervals. Sex-stratified growth curves, structural equations, and Preacher-Hayes mediation were used to estimate direct and indirect effects. β-weights were standardized. RESULTS: More LMM predicted gains in FI scores among women (β = 0.130, p < .001) and men (β = 0.089, p < .001). Conversely, more VAM and NVAM independently predicted FI decline equally among sexes (e.g., NVAM: women: β = -0.082, p < .001; men: β = -0.076, p < .001). Among women, FI associations were fully mediated by higher eosinophil counts via VAM (λ = 30.8%, p = .028) and lower lymphocyte counts via LMM (λ = 69.2%, p = .021). Among men, FI associations were partially mediated by lower basophils counts via LMM (λ = 4.5%, p = .042) and higher counts via VAM (λ = 50%, p = .037). CONCLUSION: The proportion of LMM and VAM equally influenced male FI changes over 6 years, whereas higher LMM among women appeared to more strongly influence. FI changes. Leukocyte counts strongly mediated VAM- and LMM-related FI changes in a sex-specific manner, but not for NVAM. For clinical translation, exercise studies in older adults may benefit from assessing sex-specific values of DEXA-based tissue mass, FI, and leukocyte sub-populations to gauge potential cognitive benefits of less VAM and more LMM.
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